MODULE 1: Long-Term Management of HER2-Positive Breast Cancer — Dr Krop

• Key clinical factors in the selection of neoadjuvant and adjuvant systemic therapy for HER2-positive localized breast cancer
• Published clinical research findings with postadjuvant neratinib for HER2-positive localized breast cancer; improved rates of CNS recurrence with extended adjuvant neratinib
• Dose escalation and other available approaches to mitigate neratinib-associated gastrointestinal toxicities
• Clinical factors affecting the selection and sequencing of therapy for HER2-positive metastatic breast cancer (mBC)
• Key efficacy and safety findings from the Phase III DESTINY-Breast03 trial evaluating trastuzumab deruxtecan (T-DXd) versus T-DM1 for HER2-positive mBC previously treated with trastuzumab and a taxane; implications for sequencing of therapy
• Published data sets (eg, from the HER2CLIMB, DESTINY-Breast01, DESTINY-Breast02 and NALA trials) evaluating tucatinib/trastuzumab/capecitabine, T-DXd and neratinib/capecitabine, respectively, for multiregimen-relapsed HER2-positive mBC
• Observed CNS activity with tucatinib/trastuzumab/capecitabine, T-DXd and neratinib/capecitabine in the pivotal studies leading to their approvals and other recent research efforts, such as TUXEDO-1 and DEBBRAH

MODULE 2: Optimizing the Management of ER-Positive Localized Breast Cancer — Dr Kalinsky

• Major findings from the Phase III RxPONDER trial evaluating the role of chemotherapy for ER-positive, HER2-negative breast cancer with 1 to 3 positive lymph nodes and a 21-gene Recurrence Score^® (RS) of ≤25
• Other recent studies informing the use of the 21-gene RS to guide neoadjuvant and adjuvant treatment decision-making
• Optimal selection, timing of initiation and duration of adjuvant endocrine therapy for ER-positive breast cancer; current clinical role of ovarian function suppression (OFS)/ablation for premenopausal women
• Utility of OFS as a means to preserve fertility and/or prevent chemotherapy-associated premature ovarian insufficiency among premenopausal patients
• Key efficacy and safety outcomes observed with the addition of abemaciclib to standard adjuvant hormonal therapy for patients with ER-positive, HER2-negative breast cancer at high risk for recurrence in the Phase III monarchE trial
• Current guideline-endorsed indications for adjuvant abemaciclib; identification of appropriate candidates for this strategy
• Emerging results from the Phase III NATALEE trial evaluating ribociclib as adjuvant therapy for ER-positive, HER2-negative breast cancer
• Findings with olaparib as adjuvant therapy for ER-positive breast cancer with BRCA mutations in the Phase III OlympiA study; current role of adjuvant olaparib for this patient population

MODULE 3: Considerations in the Care of Patients with ER-Positive mBC — Dr Jhaveri

• Long-term follow-up, including overall survival data, from pivotal clinical trials of palbociclib, ribociclib and abemaciclib for premenopausal and postmenopausal patients; factors affecting the selection of a CDK4/6 inhibitor and an endocrine partner for first-line treatment
• Available and emerging data sets (eg, from the RIGHT Choice, MAINTAIN, PACE, PALMIRA and SONIA trials) attempting to further define the optimal use of CDK4/6 inhibitors for ER-positive mBC
• Efficacy and safety results from the Phase III EMERALD trial evaluating the oral selective estrogen receptor degrader (SERD) elacestrant for patients with ER-positive mBC after disease progression on CDK4/6 inhibitor-based therapy
• Optimal integration of elacestrant into the current management of ER-positive mBC; importance of ESR1 mutation testing
• Incidence and clinicopathologic characteristics of ER-positive, HER2-low mBC; rationale for the clinical activity of T-DXd in patients with HER2-low disease
• Key findings from the Phase III DESTINY-Breast04 trial leading to the recent FDA approval of T-DXd for previously treated, HER2-low mBC; optimal sequencing for ER-positive disease
• Key data from the Phase III TROPiCS-02 trial evaluating sacituzumab govitecan for ER-positive, HER2-negative mBC; FDA approval and current role of sacituzumab govitecan for this patient population
• Current role of PARP inhibitors for ER-positive mBC with germline BRCA mutations
• Rationale for and available data with circulating tumor DNA (ctDNA) testing to monitor for recurrence in patients with localized breast cancer; potential clinical impact of earlier detection of relapse

MODULE 4: Novel and Emerging Strategies for ER-Positive mBC — Dr Rugo

• Biological rationale for the investigation of AKT inhibition in breast cancer; mechanism of action of capivasertib
• Key efficacy and safety data from the Phase III CAPItello-291 study evaluating capivasertib/fulvestrant versus placebo/fulvestrant for recurrent ER-positive, HER2-negative mBC
• Structural and mechanistic similarities and differences between investigational oral SERDs under development (eg, camizestrant, imlunestrant) and elacestrant
• Efficacy and safety results from the Phase II SERENA-2 study of camizestrant compared to fulvestrant for postmenopausal women with advanced ER-positive, HER2-negative breast cancer
• Available data with other oral SERDs; ongoing Phase III studies evaluating oral SERDs alone and in combination with other systemic therapies for ER-positive mBC
• Early data with novel investigational antibody-drug conjugates, such as datopotamab deruxtecan and patritumab deruxtecan, for ER-positive mBC
• Other novel agents and strategies under investigation for ER-positive mBC

MODULE 5: Evolving Clinical Decision-Making for Localized Triple-Negative Breast Cancer (TNBC) — Dr O’Shaughnessy

• Recommended approaches to biomarker assessment for localized TNBC
• Clinical and biological rationale for the investigation of immune checkpoint blockade and PARP inhibition for localized TNBC
• Available data from the Phase III KEYNOTE-522 study of neoadjuvant pembrolizumab combined with chemotherapy and continued as a single agent after surgery for high-risk, localized TNBC
• Selection of appropriate candidates for and practical implementation of (neo)adjuvant pembrolizumab
• Overall survival advantage and other key efficacy and safety findings observed with adjuvant olaparib in the Phase III OlympiA trial for high-risk, germline BRCA mutation-positive, HER2-negative breast cancer; implications for genetic testing and clinical management of localized TNBC
• Available data with and ongoing clinical research studies evaluating other PARP inhibitors or immune checkpoint inhibitors as a component of neoadjuvant or adjuvant therapy for TNBC
• Available data with and ongoing evaluation of ctDNA monitoring during and after neoadjuvant therapy as a means to better stratify risk and potentially inform further clinical decision-making
• Other novel agents and strategies under investigation for localized TNBC

MODULE 6: Recent Advances in the Treatment of Metastatic TNBC (mTNBC) — Prof Schmid

• Efficacy and safety findings with pembrolizumab/chemotherapy for previously untreated, PD-L1-positive mTNBC; optimal integration into practice
• Published data evaluating the utility of ctDNA testing to assess immunotherapy response in patients with mTNBC; potential role of this strategy
• Key clinical research findings guiding the use of PARP inhibitors for mTNBC
• Available findings with and current role of PARP inhibitor monotherapy for patients with mBC harboring germline or somatic mutations in DNA damage response pathway genes beyond germline BRCA1/2
• Outcomes reported with T-DXd among patients with ER-negative, HER2-low mBC in the DESTINY-Breast04 study; optimal sequencing of T-DXd opposite other available treatment options
• Key efficacy and safety findings from the Phase III ASCENT trial comparing sacituzumab govitecan to physician’s choice of chemotherapy for relapsed/refractory mTNBC; integration into current clinical practice
• Available efficacy and safety findings with and ongoing investigation of other antibody-drug conjugates, including datopotamab deruxtecan and patritumab deruxtecan, for mTNBC
• Other novel agents and strategies under investigation for advanced TNBC